Registration Dossier

Administrative data

Description of key information

Oral (OECD 401): LD50 values > 5000 mg/kg bw
Inhalation (OECD 436): LC50 > 5.7 mg/L air
Dermal: no data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute inhalation toxicity of isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). In order to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of acute toxicity

CAS

Chemical name

Molecular weight

Acute toxicity Oral

Acute toxicity inhalation

Acute toxicity dermal

111937-03-2 (a)

Isononanoic acid, C16-18 alkyl esters

382.66; 410.72

Experimental result:
LD50 >5000 mg/kg bw (mouse)
LD50 >17010 mg/kg bw (rat)

RA: CAS 26399-02-0

Waiving

26399-02-0 (b)

2-ethylhexyl oleate

394.67

Experimental result:
LD50 >5000 mg/kg bw (mouse)

Experimental result:
LC50 >5.7 mg/L air (analytical)

--

(a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Acute oral toxicity

CAS 111937-03-2

In a study comparable to OECD 401, 5 female mice were administered 5000 mg/kg bw isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) (Dufour, 1991). No mortality occurred. No clinical signs were observed and the body weight was not affected during the 7-day observation period. No necropsy examinations were performed at sacrifice. The LD50 is considered to be > 5000 mg/kg bw.

In a study performed by Potokar (1970), 10 male rats/dose were administered 10 mL/kg bw isononanoic acid, C16-18 alkyl esters as a 50% solution of the test substance in olive oil and 19.9 mL/kg bw of the undiluted test substance (equivalent to 8.55 and 17.01 g/kg bw, respectively). No mortality occurred, and no clinical signs were reported during the 7-day observation period. Based on the limited data available, the LD50 is considered to be > 17.01 g/kg bw. 

Acute inhalation toxicity

CAS 26399-02-0

The acute inhalation toxicity of 2-ethylhexyl oleate (CAS 26399-02-0) was assessed in a study performed according to OECD 436 (Van Huygevoort, 2010). 3 rats/sex were exposed to 5.7 ± 0.4 mg/L (actual concentration) of the test substance as an aerosol via nose-only exposure for 4 hours. The nominal concentration was 15.4 mg/L and the MMAD was 2.1-2.5 µm. No mortality occurred. The animals had a hunched posture on Day 2; no further clinical signs were observed during the 14-day study period. The body weight gain was within the range that is normal for this strain and study type. No findings were reported during the macroscopic examination. The LC50 is considered to be > 5 mg/L.

Acute dermal toxicity

This information is not available.

Conclusions for acute toxicity

The available acute oral toxicity data showed that no mortality occurred and the LD50 was > 5000 mg/kg bw. No mortality was observed in the acute inhalation study, leading to an LC50 of > 5 mg/L (Van Huygevoort, 2010). There are no data available on the acute dermal toxicity of isononanoic acid, C16-18 alkyl esters. However, the physicochemical properties of the substance (molecular weight: 382.66-410.72 g/mol, log Pow > 6, water solubility < 0.05 mg/L) are in a range that anticipate a lower dermal absorption rate than via the oral and inhalation route. Since the substance is neither acute toxic by the oral route (LD50 > 5000 mg/kg bw) nor skin or eye irritating and there are no indications for a skin sensitising potential, it is unlikely that acute dermal exposure would lead to toxic effects at dose levels lower than the oral LD50. Therefore, testing for acute toxicity by the dermal route is also deemed scientifically unjustified in accordance with Annex XI, Section 1.2 of Regulation (EC) 1907/2006, based on the weight of evidence from the available physicochemical and toxicological data documented in the technical dossier and the Chemical Safety Report. Hence, further testing on vertebrate animals for this property shall be omitted.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.


Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance-specific studies and read-across from structurally similar substances, the available data on the acute oral and inhalation toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on acute dermal toxicity.